Suckling initiates a neuroendocrine reflex which releases oxytocin (OT) from the axon terminals of neurons in the supraoptic and paraventricular nuclei (SON/PVN) into the general circulation. Little, however, is known to date about the neurochemical mechanisms involved. The purpose of the proposed investigation is to elucidate the facilitatory and inhibitory neurochemical mechanisms controlling OT secretion in response to suckling in the rat, with emphasis on the roles of catecholamines and opioid peptides both at the level of the CNS and at the level of the neural lobe (NL). Reliance will be placed upon direct analysis of OT concentrations in the plasma using RIA rather than intramammary pressure or milk ejection, which are indirect indices of OT release. Two specific interrelated hypotheses will be tested: 1) Suckling activates central noradrenergic systems that regulate OT release via actions in the SON/PVN and/or in other hypothalamic areas that influence these neurosecretory centers. 2) The release of OT in response to suckling is modulated in the NL a) by dopamine (DA) released from tuberohypophysial axons, b) by endogenous opioid neuropeptides which may serve as transmitters with OT, and c) by circulating norepinephrine (NE) and epinephrine (E) of sympathetic adrenal origin. (Epinephrine is released from the sympathetic-adrenal system into the circulation of the rat in response to suckling.) We will investigate these hypotheses in vivo by determining a) whether suckling affects the turnover of DA, NE, and serotonin (5H-T) in discrete areas of the brain and in the NL; b) whether localized depletions of brain monoamines by the neurotoxins, 6 hydroxydopamine (for NE and DA) and 5, 7 dihydroxytryptamine (for 5H-T), affect the suckling-induced release of OT; c) the effects of centrally and peripherally active monoamine agonists and antagonists and of adrenalectomy upon OT release during suckling; d) the effects of opiate agonists and antagonists and of opioid neuropeptides upon OT release during suckling; and e) whether opiates influence the changes in brain and NL catecholamine turnover induced by suckling. We will also employ in vitro methods (isolated NL and NL synaptosomes) to analyze the effects of monoaminergic and opiate agonists and antagonists upon OT secretion directly at the NL.